One piece of evidence potentially contradicting a protective role of sTREM2 in AD, is that the H157Y mutation of TREM2 expressed in cells significantly increased sTREM2 shedding relative to wild-type TREM2, resulting in increased sTREM2 and decreased full-length TREM2, but is associated with increased AD risk (Schlepckow et al., 2017; Thornton et al., 2017). Here, TREM2 is linked to Alzheimer disease.